Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels aft;er pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GK secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2 +/- 1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5 +/- 1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, iv), with a peak GH secretion of less than 3 mu g/L. Two tests were carried out. On one day, they were given GHRH (100 mu g, iv, 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 pg, iv, 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (mu g/L) of 23.8 +/- 4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7 +/- 14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (mu g/L) of 3.9 +/- 1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0 +/- 3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (mu g/L) of 2 +/- 0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3 +/- 1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3 +/- 1.1), compared with obese patients (mean peak, 16.0 +/- 3.2) (P < 0.05) and control subjects (mean peak, 54.7 +/- 14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.